Vesicular stomatitis virus (VSV), a member in the rhabdoviridae family, causes a contagious disease in horses, cattle, pigs, sheep and goats, characterized by vesicular lesions on the tongue, oral mucosa and udder. VSV is transmitted by arthropod vectors. The prominent clinical presentation of vesicular stomatitis is the development of vesicles and ulcers in the oral cavity and, less frequently, on the teats and coronary bands. Mortality rates are typically very low, but production suffers because affected animals lose weight and may develop lameness or mastitis. The most significant concern with vesicular stomatitis is that, in cattle and pigs, it is clinically indistinguishable from foot and mouth disease and swine vesicular disease. Consequently, outbreaks of vesicular stomatitis lead to rapid imposition of international quarantines and shutoff of trade of animals and animals products.
There is also public health concern because humans can be infected, Patterson, W. C., et al., J. Am. Vet. Med. Ass., 133, 57 (1958), and the virus may be spread by insect vectors, Ferris et al., J. Infect. Dis., 96, 184 (1955), Tesh et al., Science, 175, 1477 (1972).
VSV contains a single negative strand of ribonucleic acids (RNA), which encodes 5 messenger RNA's (mRNA's) and 5 known proteins, the nucleocapsid protein (N protein), the non-structural phosphoprotein (P protein or NS protein), the matrix protein (M protein), the G glycoprotein and the large polymerase protein (L protein). Two VSV serotypes, Indiana (VSVI) and New Jersey (VSVNJ), are known. Although the diseases caused by the two VSV serotypes are similar, they are immunologically distinct and are found in separate enzootic areas within the Western Hemisphere. Complementary desoxyribonucleic acids (DNA) copies of mRNA for the G, M, N, and NS proteins of VSVI have been cloned and sequenced (J. K. Rose et al., J. Virol., 39, 519 (1981); C. J. Gallione et al., J. Virol., 39, 529 (1981); C. J. Gallione et al., J. Virol., 46, 162 (1983). The G and N genes of the Indiana serotype have been expressed in eukaryotic cells (J. K. Rose et al., Cell, 30, 753 (1982); J. Sprague et al., J. Virol., 45, 773 (1983)). The sequence of the VSVNJ virus is reported in Gallione, C. J. and Rose, J. K., Journal of Virology 46, 162-169 (1983). This publication also reports the isolation of VSVNJ cDNA, including that corresponding to the genome segment, which encodes the G protein.
VSV are available before the American Type Culture Collection (ATCC), 12301 Parklawn Drive, Rockville, Md. 20852, USA. Notably, VSV of New Jersey serotype have been deposited at the ATCC under accession numbers No. VR-1239, and VR-159, and VSV of Indiana serotype under ATCC accession numbers No. VR-1238, VR-1415 to VR-1419 and VR-1421.
Nucleic acid sequences and amino acid sequences of the VSVNJ and VSVI have been published in various publications (i.e. Rose et al., Cell, 1980, 19(2): 415-421) and are also available in the NCBI database (i.e. accession numbers No. J02428, NC—001560).
Intranasal instillation of either serotype in mice can lead to lethal infections (Sabin and Olitsky, J. Exp. Med., 1937, 66: 15-34; Sabin and Olitsky, J. Exp. Med., 1938, 67: 201-227).
The only vaccine currently available for the control of vesicular stomatitis is an inactivated preparation (Bachmann et al., Med. Microbiol. Immunol., 1994, 183(2): 95-104; House et al., Vaccine, 2003, 21(17-18): 1932-1937). Use of this vaccine is restricted to states with confirmed cases of vesicular stomatitis or which are considered risky for incursion of the disease (Cantlon et al., Vaccine, 2000, 18: 2368-2374). Because this vaccine consists of whole virus, immunized animals are serologically indistinguishable from those that have been infected, and its widespread use is incompatible with effective surveillance of this disease. What is clearly needed for control of vesicular stomatitis is a vaccine that confers protective immunity, yet allows unambiguous differentiation of vaccinates from animals naturally infected with the viruses. Cantlon et al. (Cantlon et al., Vaccine, 2000, 18: 2368-2374) on the basis of plasmids, constructed in vivo expression vectors containing VSVNJ G gene under the control of the immediate early promoter from human cytomegalovirus. These plasmids were administered with immunostimulatory CpG-containing oligonucleotides and optionally with a plasmid expressing mouse interleukin-2 (mIL2) to mice in order to evaluate the immune response with respect to neutralizing antibody titer and mortality results. Neutralizing antibody titers were also observed on horses and cattle after plasmid administrations.
Mackett et al. (Mackett et al., Science, 1985, 227, 433-435) on the basis of the vaccinia virus, constructed in vivo expression vectors containing various inserts corresponding to nucleotide sequences encoding for proteins G of VSVNJ or G of VSVI or N of VSVI. These recombinant viral vectors were administered to mice and cattle to evaluate the immune response with respect to neutralizing antibody titer and mortality results or clinical signs. The cattle vaccinated with recombinant vaccinia virus encoding G of VSVNJ developed significant VSV neutralization titers. However, all the cows developed lesions after 103 PFU VSV challenge.
It would be advantageous to provide improved immunogenic and vaccine compositions against VSV, and methods for making and using such compositions, including such compositions that provide for differential diagnostic methods.
Citation or identification of any document in this application is not admission that such document is available as prior art to the present invention.